Analyses of frequency profiles of markers on disease or drug-response related genes in diverse populations are important for the dissection of common diseases. We report the results of analyses of data on 405 SNPs from 75 such genes and a 5.2 Mb chromosome, 22 genomic region in 1871 individuals from diverse 55 endogamous Indian populations. These include 32 large (>10 million individuals) and 23 isolated populations, representing a large fraction of the people of India. We observe high levels of genetic divergence between groups of populations that cluster largely on the basis of ethnicity and language. Indian populations not only overlap with the diversity of HapMap populations, but also contain population groups that are genetically distinct. These data and results are useful for addressing stratification and study design issues in complex traits especially for heterogeneous populations.

Considering the application of human genome variation databases in precision medicine, population‐specific genome projects are continuously being developed. However, the Middle Eastern population is underrepresented in current databases. Accordingly, we established Iranome database (http://www.iranome.com) by performing whole exome sequencing on 800 individuals from eight major Iranian ethnic groups representing the second largest population of Middle East. We identified 1,575,702 variants of which 308,311 were novel (19.6%). Also, by presenting higher frequency for 37,384 novel or known rare variants, Iranome database can improve the power of molecular diagnosis. Moreover, attainable clinical information makes this database a good resource for classifying pathogenicity of rare variants. Principal components analysis indicated that, apart from Iranian‐Baluchs, Iranian‐Turkmen, and Iranian‐Persian Gulf Islanders, who form their own clusters, rest of the population were genetically linked, forming a super‐population. Furthermore, only 0.6% of novel variants showed counterparts in “Greater Middle East Variome Project”, emphasizing the value of Iranome at national level by releasing a comprehensive catalog of Iranian genomic variations and also filling another gap in the catalog of human genome variations at international level. We introduce Iranome as a resource which may also be applicable in other countries located in neighboring regions historically called Greater Iran (Persia).

Repositioning of the global epicentre of non-optimal cholesterol NCD Risk Factor Collaboration (NCD-RisC)* High blood cholesterol is typically considered a feature of wealthy western countries 1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world 3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health 4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low-and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium,

Pre-eclampsia, a life-threatening disease during pregnancy, is a leading cause of global maternal mortality. Although there is substantial evidence of a genetic background, the complexity of the processes involved and nature of the maternal-fetal phenomenon do not make the search for the causative genes easy. Recent retrospective studies on the subject suggest the heritable allelic variations, particularly the utero-placental renin-angiotensin system with defective placental vascular development, could become the cornerstone for the genetics of pre-eclampsia and hence might well be associated with such defective development. Moreover, the role of immune mechanisms (immune maladaptation) deserves not to be ignored. Large-scale studies entailing genomewide scanning, sib-pair linkage analysis, and family-based association studies with appropriate power to detect genes with a lower relative risk are necessary to understand the puzzle of the disease. Moreover, recently, the importance of epigenetic features and the effect of imprinted genes related to trophoblast growth as well as fetal development on hypertension in pregnancy have been highlighted. All these possibilities are intuitively attractive and are supported by some circumstantial evidence. Although the consistent tenor of a series of papers instill some confidence, we need meticulously designed larger-scale investigations including large numbers of affected women and their babies to provide the analytic stringency essential to study the polygenic multifactorial basis of pre-eclampsia.

Hepatitis B virus (HBV) is a significant public health problem and a leading cause of morbidity and mortality, and approximately 30% of the world's population is infected with HBV. The objective of our study was to determine the seroprevalence of HBV and major risk factors associated with its occurrence. Four thousand eighty-seven healthy Iranian subjects aged 8-80 years were screened for HBV serological markers by an enzyme immunoassay method. A structured questionnaire was administered to all participants. Multiple logistic regression, an unpaired t-test for continuous data and the χ (2) test for categorical data were performed. A total of 4087 participants were tested for hepatitis B surface antigen (HBsAg), of which 62 (1.5%) were seropositive. Fifteen percent of the subjects were positive for anti-HBs, 6.3% were positive for isolated anti-HBc and 12.5% were positive for both anti-HBs and anti-HBc. Laborers showed a higher HBsAg(+) seroprevalence and risk compared with jobless participants (Pearson's = 8.276, P = 0.004; OR = 4.1, 95% CI: 1.5-11.2). Bivariate logistic regression revealed that the following variables were significantly associated with HBV seropositivity: phlebotomy (P = 0.002; OR = 5.0, 95% CI: 2.1-11.9), tattooing (P = 0.003; OR = 3.4, 95% CI: 1.6-7.0), intravenous drug use (P = 0.001; OR = 2.4, 95% CI: 1.4-4.1). The adjusted prevalence ratios remained significantly associated with HBV seropositivity and thus likely served as possible risk factors for HBV. The overall positive seroprevalence was 1.5%. Among the variables, only phlebotomy, tattooing and intravenous drug injection emerged as major potential risk factors for hepatitis B infection and responsible for transmission of the disease.

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BackgroundImmunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness.ObjectivesThe aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments.Materials and MethodsHepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database.ResultsAll strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively.ConclusionsRT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level.